Song In Hye, Kim Young-Ae, Heo Sun-Hee, Park In Ah, Lee Miseon, Bang Won Seon, Park Hye Seon, Gong Gyungyub, Lee Hee Jin
1 Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
2 Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Tumour Biol. 2017 Oct;39(10):1010428317734816. doi: 10.1177/1010428317734816.
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data. Among the 681 triple-negative breast cancer patients, 45.8% demonstrated high ADAR1 expression. Tumours with high ADAR1 expression exhibited high tumour-infiltrating lymphocyte levels, considerable CD8 + T lymphocyte infiltration, high histological grade and high expression of interferon-related proteins, including HLA-ABC, MxA and PKR. Among patients with lymph node metastasis, those with high tumour-infiltrating lymphocyte levels and low ADAR1 expression demonstrated the best disease-free survival. The Cancer Genome Atlas data analysis of basal-like tumours revealed significant positive correlation between ADAR1 and CD8B expression and positive association of high ADAR1 expression with immune responses and apoptosis pathways. We detected high ADAR1 expression in half of the triple-negative breast cancer patients. In addition to DNA mutations, RNA editing can be related to neoantigens; hence, we need to explore non-synonymous mutations exclusively found using RNA sequencing data to identify clinically relevant neoantigens.
具有高突变负荷的肿瘤表现出大量新抗原和肿瘤浸润淋巴细胞。ADAR1介导的RNA编辑是表位变化的一个来源。然而，三阴性乳腺癌中癌细胞的ADAR1表达和肿瘤浸润淋巴细胞水平尚未得到充分评估。我们通过免疫组化检测了681例三阴性乳腺癌患者的ADAR1表达，并分析了其临床病理特征。我们还使用癌症基因组图谱数据对基底样肿瘤进行了分析。在681例三阴性乳腺癌患者中，45.8%表现出ADAR1高表达。ADAR1高表达的肿瘤表现出高肿瘤浸润淋巴细胞水平、大量CD8 + T淋巴细胞浸润、高组织学分级以及包括HLA-ABC、Mx A和PKR在内的干扰素相关蛋白的高表达。在有淋巴结转移的患者中，肿瘤浸润淋巴细胞水平高且ADAR1表达低的患者无病生存期最佳。对基底样肿瘤的癌症基因组图谱数据分析显示，ADAR1与CD8B表达之间存在显著正相关，且ADAR1高表达与免疫反应和凋亡途径呈正相关。我们在一半的三阴性乳腺癌患者中检测到ADAR1高表达。除了DNA突变外，RNA编辑可能与新抗原有关；因此，我们需要探索仅使用RNA测序数据发现的非同义突变，以识别临床相关的新抗原。
